Intravenous thrombolytic remedy, percutaneous coronary intervention, and emergency coronary artery bypass grafting have considerably improved the restoration of blood movement and oxygen provide to ischemic myocardial tissue, markedly decreasing acute mortality fee in sufferers with myocardial infarction (MI). [1], [2] Nevertheless, reperfusion itself can set off oxidative stress, irritation, and secondary necrosis, resulting in myocardial ischemia-reperfusion harm (MIRI), and exacerbating ischemic injury. [3] Regardless of the event of pharmacological interventions—similar to anti-inflammatory brokers, antioxidants, and calcium antagonists—their scientific efficacy stays restricted and controversial. [4], [5]
The overproduction of mitochondrial ROS throughout reperfusion is a key driver of MIRI. [6] Throughout ischemia, succinate accumulates and is quickly oxidized by succinate dehydrogenase (SDH) upon reperfusion, resulting in a burst of ROS and calcium overload through reverse electron transport (RET). [7], [8] This cascade ends in the opening of the mitochondrial permeability transition pore (mPTP), additional amplifying ROS launch and triggering cardiomyocyte apoptosis, establishing a vicious cycle of oxidative injury and cell dying. [9], [10]
Lately, pure antioxidants—similar to superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), tocopherols, and flavonoids—have been explored for MIRI therapy. [11], [12] Nevertheless, their scientific utility is proscribed by poor pharmacokinetics and potential unwanted effects. Advances in nanotechnology have revealed that inorganic nanoparticles, as soon as thought of biologically inert, can mimic enzymatic exercise, providing a promising various to pure antioxidants. A wide range of metallic and metallic oxide nanomaterials, together with Fe, Ir, Mn, Pt, Co, CeO₂, and Mn₃O₄, have been demonstrated to own SOD or CAT-like actions. [13], [14], [15] In contrast with pure enzymes, nanozymes has some great benefits of purposeful variety, excessive stability and straightforward preparation, which provides them distinctive advantages in antioxidant remedy. Amongst nanozymes, CeO₂ is especially notable for its antioxidant properties, pushed by the combined valence states of Ce³ ⁺ and Ce⁴⁺ on its floor. [16] This distinctive characteristic facilitates oxygen loss and electron acquire, creating oxygen vacancies and enabling repeated ROS scavenging. [17], [18] Research have proven that CeO₂ nanoparticles scale back oxidative stress and irritation, defending in opposition to coronary heart injury. [19], [20] For instance, Jiang et al. demonstrated that CeO₂ nanospheres mixed with curcumin mitigate sepsis-induced myocardial harm by inhibiting iron-mediated apoptosis. [21] Moreover, bimetallic nanoparticles, which exhibit enhanced catalytic efficiency as a result of ensemble results, symbolize a promising avenue for creating superior enzyme-mimics. [22]
Regardless of well timed reperfusion, subendocardial blood provide insufficiency typically persists, exacerbated by ROS-induced vascular harm and irritation, which contribute to the non-reflow phenomenon. [23], [24], [25] Angiogenesis—the formation of latest microvascular networks—presents a possible answer by enhancing perfusion and enhancing cardiac operate. Ion-doped bioactive supplies, similar to these incorporating strontium (Sr²⁺), have demonstrated anti-inflammatory and angiogenic properties. [26] Sr²⁺ promotes endothelial cell proliferation and upregulates pro-angiogenic elements like VEGF, bFGF, and MMP-2, whereas additionally modulating macrophage phenotypes to reinforce vascularization. [27], [28] These properties make Sr²⁺-doped nanoparticles a promising device for selling tissue regeneration.
On this examine, we developed Sr2+-doped ceria nanoparticles (CeSr NP) utilizing a sol-gel response, with oleylamine as a structure-directing agent. The nanoparticles had been encapsulated in mPEG2000-DSPE micelles and functionalized with Cxcr4-overexpressing bone marrow-derived mesenchymal stem cell (bMSC) membranes (CSPM+). This design permits focused supply to infarcted areas through the SDF-1 gradient, selling myocardial restore and angiogenesis (Scheme 1). To guage the antioxidative and pro-angiogenic results of CSPM+ in MIRI, a mouse mannequin was established by coronary artery ligation and reperfusion. ROS ranges, ventricular reworking index, cardiac operate parameters, and neovascularization markers had been assessed. Moreover, potential signaling pathways had been explored to elucidate the underlying mechanisms of CSPM+ in treating MIRI.
